Slobodan Milutinović1, Vladimir Trkulja. 1. Department of Nephrology and Dialysis and Clinical Pharmacology Unit, Holy Ghost General Hospital, Zagreb, Croatia.
Abstract
AIM: To determine if temporary discontinuation of epoetin therapy in anemic patients with end stage renal disease (ESRD) influences their responsiveness to epoetin. METHODS: We performed a post hoc analysis of the data from two consecutive single-center randomized trials (T1 and T2) comparing the efficacy of two epoetin products (E1 and E2) in anemic patients with ESRD. The analysis included a subset of 44 patients who participated in both trials and were not receiving epoetin in the period (median, 12 months; range 5-15) between the trials due to epoetin shortage. Two co-primary outcomes were average weekly hemoglobin difference from the baseline and average weekly epoetin dose. RESULTS: With adjustment for potential differences between E1 and E2, average weekly hemoglobin difference of 1.21 g/dL from the baseline was lower in T2 than that of 1.71 g/dL in T1: difference -0.49 (95% confidence interval [CI], -0.68 to -0.29; P<0.001). Average weekly epoetin dose of 107 IU/kg in T2 was higher than 96 IU/kg in T1 (ratio, 1.13; 95% CI, 1.04-1.24; P=0.009). With additional adjustment for within-subject changes in baseline covariates from T1 to T2 (baseline hemoglobin, body mass index, serum albumin, ferritin and transferrin saturation, intact parathormone, C-reactive protein, dialysis dose, and use of angiotensin converting enzyme inhibitors), hemoglobin response remained lower (adjusted difference, -0.44 g/dL; 95% CI, -0.73 to -0.16; P=0.004) and weekly epoetin dose remained higher in T2 than inT1 (adjusted ratio, 1.17; 95% CI, 1.03-1.34; P=0.016). CONCLUSIONS: In patients with ESRD, responsiveness to epoetin was lower in T2 after a period of epoetin therapy discontinuation than in T1 epoetin trial. Since this could not be explained by within-subject changes in factors known to affect response to epoetin, a prolonged withdrawal of epoetin in patients with ESRD might independently contribute to a reduced responsiveness to epoetin at a later re-exposure. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier for T1 trial: NCT00322413.
RCT Entities:
AIM: To determine if temporary discontinuation of epoetin therapy in anemicpatients with end stage renal disease (ESRD) influences their responsiveness to epoetin. METHODS: We performed a post hoc analysis of the data from two consecutive single-center randomized trials (T1 and T2) comparing the efficacy of two epoetin products (E1 and E2) in anemicpatients with ESRD. The analysis included a subset of 44 patients who participated in both trials and were not receiving epoetin in the period (median, 12 months; range 5-15) between the trials due to epoetin shortage. Two co-primary outcomes were average weekly hemoglobin difference from the baseline and average weekly epoetin dose. RESULTS: With adjustment for potential differences between E1 and E2, average weekly hemoglobin difference of 1.21 g/dL from the baseline was lower in T2 than that of 1.71 g/dL in T1: difference -0.49 (95% confidence interval [CI], -0.68 to -0.29; P<0.001). Average weekly epoetin dose of 107 IU/kg in T2 was higher than 96 IU/kg in T1 (ratio, 1.13; 95% CI, 1.04-1.24; P=0.009). With additional adjustment for within-subject changes in baseline covariates from T1 to T2 (baseline hemoglobin, body mass index, serum albumin, ferritin and transferrin saturation, intact parathormone, C-reactive protein, dialysis dose, and use of angiotensin converting enzyme inhibitors), hemoglobin response remained lower (adjusted difference, -0.44 g/dL; 95% CI, -0.73 to -0.16; P=0.004) and weekly epoetin dose remained higher in T2 than inT1 (adjusted ratio, 1.17; 95% CI, 1.03-1.34; P=0.016). CONCLUSIONS: In patients with ESRD, responsiveness to epoetin was lower in T2 after a period of epoetin therapy discontinuation than in T1 epoetin trial. Since this could not be explained by within-subject changes in factors known to affect response to epoetin, a prolonged withdrawal of epoetin in patients with ESRD might independently contribute to a reduced responsiveness to epoetin at a later re-exposure. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier for T1 trial: NCT00322413.
Authors: Francesco Locatelli; Conrad A Baldamus; Giuseppe Villa; Alexandru Ganea; Angel L Martín de Francisco Journal: Am J Kidney Dis Date: 2002-07 Impact factor: 8.860
Authors: Walter H Hörl; Yves Vanrenterghem; Bernard Canaud; Johannes Mann; Ugo Teatini; Christoph Wanner; Björn Wikström Journal: Nephrol Dial Transplant Date: 2005-05 Impact factor: 5.992
Authors: Suetonia C Palmer; Valeria Saglimbene; Dimitris Mavridis; Georgia Salanti; Jonathan C Craig; Marcello Tonelli; Natasha Wiebe; Giovanni F M Strippoli Journal: Cochrane Database Syst Rev Date: 2014-12-08